Antibodies are a class of globular proteins which are produced by the immune system as a defense against foreign agents in mammalian systems. These proteins bind their respective antigen or hapten through a collection of non-covalent interactions (hydrophobic, electrostatic and/or hydrogen bonding interactions). The strength of binding between the antigen and the antibody can vary due to the natural elimination or addition of some of these interactions and the resulting affinity constant (Ka) generally varies between about 10.sup.3 and about 10.sup.10.
Monoclonal antibodies are a subset of antibodies, and are proteins with a single defined structure and defined amino acid sequence. Monoclonal antibodies are known and desired primarily for their specificity of binding; that is their ability to bind only one compound (antigen or hapten) out of many with very similar structures. However, a recurring problem is the identification and isolation of monoclonal antibodies which have not only great specificity, but also high affinity, i.e. tight binding to its antigen or hapten. Monoclonal antibodies with both high specificity and high affinity are generally identified and isolated only by very laborious screening of many hybridoma cell cultures. Alternatively, genetic techniques may be used to alter specific amino acids in the antibody sequence by site-directed mutagenesis or to generate large numbers of mutations for screening purposes by producing libraries of mutations. However, these techniques are also very labor intensive.
Chemical modification of antibodies with antigen-based reagents has been utilized to produce catalytic antibodies as taught in PCT Application WO 90/05749 published May 31, 1990 and U.S. Pat. No. 5,215,889. However, the chemical modifications used to produce catalytic antibodies are specifically defined as functionalities which do not substantially affect binding affinity between the antibody and its antigen.